Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease

The objective of this study was to evaluate the efficacy and safety of low-dose substrate balance therapy with OGT 918 for the treatment of adults with Gaucher disease. Eighteen patients with Gaucher disease from two centers were enrolled in an open-label 6-month study of OGT 918, 50 mg taken three times daily (TID), followed by an optional extended-use phase. Changes in liver and spleen volume at 6 and 12 months, as well as routine hematological and biochemical parameters on a monthly basis, were evaluated. During the extension, dosage was increased to 100 mg TID in patients in one center to improve the response. Seventeen patients completed 6 months; of 16 patients in the extension phase, 13 were evaluable at 12 months. Percentage changes in liver (-5.9%, P = 0.007) and spleen (-4.5%, P = 0.025) volumes and in chitotriosidase levels (-4.6%, P = 0.039) at 6 months were commensurately lower than those reported previously in an open-label trial using 100 mg TID; hemoglobin and platelet counts were not boosted. At 12 months there were further mean decreases from baseline in liver volume (-6.2%, P = 0.037), spleen volume (-10.1%, P < 0.05), and chitotriosidase levels (-15.3%, P < 0.05) as well as mean changes of +1.2 and +14.7% in hemoglobin and platelet concentrations, respectively [correction]. There were no serious adverse effects throughout the 6-month study period; common side effects were diarrhea (94%) and weight loss (67%), comparable to the incidence in the original trial. We conclude that OGT 918 was safe and effective at 50 mg TID, but shows dose dependency in ameliorating parameters of Gaucher disease relative to the results noted in the seminal trial; there was no improvement in the rate of hematological response and no reduction in side effects. Results from the extension wherein some patients were dose increased suggest that 100 mg TID should be the preferred starting regimen for patients with symptomatic type I Gaucher disease.